In an international prospective cohort study (EMBRACE-I) reported in The Lancet Oncology, Pötter et al found that magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy was associated with a high rate of long-term local disease control and relatively low cumulative severe morbidity in women with locally advanced cervical cancer.
Study Details
The study involved prospectively collected data from 24 sites in Europe, Asia, and North America on patients with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients had to have International Federation of Gynecology and Obstetrics (FIGO) stage IB to IVA disease or stage IVB disease restricted to para-aortic lymph metastasis below the L1–L2 interspace considered suitable for curative treatment.
Treatment consisted of chemoradiotherapy with weekly cisplatin at 40 mg/m² on 1 day per cycle for five to six cycles and 45 to 50 Gy of external-beam radiotherapy delivered in 1.8 to 2 fractions followed by MRI-based image-guided adaptive brachytherapy. The primary outcome measures were local control and late morbidity.
Key Findings
KEY POINTS
- At a median follow-up of 51 months, actuarial overall 5-year local control was 92%.
- Rates according to FIGO stage ranged from 89% in IIA2 and IVB to 98% in IB1 and 100% in IIIA.
- The actuarial cumulative 5-year incidence of grade 3 to 5 morbidity was 14.6%.
Data from 1,341 patients were available for analysis of disease response, and data from 1,251 were available for assessment of morbidity. MRI-based image-guided adaptive brachytherapy with dose optimization was performed in 1,317 patients (98.2%). Median high-risk clinical target volume was 28 cm³ (interquartile range [IQR] = 20–40 cm3), and median minimal dose to 90% of the clinical target volume was 90 Gy (IQR = 85–94 Gy) equieffective dose in 2 Gy per fraction.
At a median follow-up of 51 months (IQR = 20–64 months), actuarial overall 5-year local control was 92% (95% confidence interval [CI] = 90%–93%). Rates according to FIGO stage ranged from 89% in IIA2 and IVB to 98% in IB1 and 100% in IIIA (n = 13; P = .31 across stages).
Five-year pelvic control was 87% (95% CI = 85%–89%); 5-year nodal control was 87% (95% CI = 85%–89%); 5-year overall survival was 74% (95% CI = 72%–77%); and 5-year disease-free survival was 68% (95% CI = 65%–70%).
The actuarial cumulative 5-year incidence of grade 3 to 5 morbidity was 14.6%, including 6.8% for genitourinary events, 8.5% for gastrointestinal events, 5.7% for vaginal events, and 3.2% for fistulae. Apart from fistulae, the most common individual events were gastrointestinal stenosis (2.8%), gastrointestinal bleeding (2.2%), diarrhea (1.9%), ureteric strictures (2.9%), urinary incontinence (2.2%), urinary frequency (1.8%), cystitis (1.3%), vaginal stenoses (4.0%), and vaginal mucositis (1.4%).
The investigators concluded, “Chemoradiotherapy and MRI-based image-guided adaptive brachytherapy result in effective and stable long-term local control across all stages of locally advanced cervical cancer, with a limited severe morbidity per organ. These results represent a positive breakthrough in the treatment of locally advanced cervical cancer, which might be used as a benchmark for clinical practice and all future studies.”
Maximilian Paul Schmid, MD, of the Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Medical University of Vienna, Aarhus University Hospital, Elekta AB, and Varian Medical Systems. For full disclosures of the study authors, visit thelancet.com.
